Project Summary/Abstract The degree of behavioral control that an organism (rodent to human) can exert over an adverse event is arguably the most potent variable yet discovered that modulates the behavioral and neurochemical impact of that event. When the organism does have an element of control, the behavioral and neurochemical sequelae of the adverse event are blunted or eliminated. Importantly, the experience of control not only blunts the impact of the stressor being controlled, but also blunts the impact of stressors experienced much later (at least one month), that is, control produces future resilience in the face of adversity. Recent research has extended the study of the impact of experiencing control to determining whether future fear processes might be altered. Indeed, the experience of control reduces future fear conditioning, facilitates future fear extinction and prevents the spontaneous recovery of fear. In addition, we have extended the study of controllability phenomena to females, and surprisingly, here control does not blunt the impact of stressors or alter later fear conditioning. The proposed research focuses on the roles of specific prefrontal cortex circuits in mediating the effects of control on fear processes, as well as a determination of exactly how critical prefrontal circuits may respond to stressors differently in males and females.